Candida albicans is a commensal that colonizes skin and mucosal surfaces including the oral cavity. The organism forms biofilms on mucosa and oral devices, e.g. dentures, generally in association with bacteria. The organism is also an agent of opportunistic infection of these surfaces as well as disseminated disease. Among individuals that are most susceptible to oral infection are HIV+ patients who have declining CD4+ T cells. The correlation between loss of this lymphocyte population and disease implicates CD4+ T cells in protection of the healthy individual from disease. CD4+ T cells have also been implicated in susceptibility in murine models of infection. While T-helper 1 type cell-mediated immunity (CMI) has been implicated in protection and recovery from both systemic and mucosal infection, it is also clear that mucosal and systemic immune response has elements of compartmentalization. This is emphasized by the susceptibility of the AIDS patient to oral mucosal but not systemic disease. The profile of T cells in the oral mucosa differs from that of peripheral blood. In recent years, T cells clones have been a useful tool to identify the specific antigens and their epitopes that stimulate the CMI response. However, the application of these protocols has been applied to lymphocytes of peripheral circulation and not those of the oral mucosa that are important in the response to oral pathogens. The goal of this proposal is to establish procedures for isolating CD4+ T cell clones that are derived from the T cell population of the oral mucosa in mice colonized with C. albicans. The successful development of this protocol has specific application that will provide a major tool for subsequent studies of host response and control of oral C. albicans. A successful protocol will also have more widespread application to study the mucosal response to components of the normal oral flora and agents of oral infection.